Titanium dioxide in food linked to gut health effects

Research linking the use of titanium dioxide as a food additive to gut inflammation and bowel cancer in rats, has prompted the French government to initiate further analysis into the substance.

The findings add a new dimension to the ongoing debate over a French proposal to set a mandatory EU category 1B inhalation carcinogen classification for titanium oxide – something which, if adopted, could have major implications for many downstream sectors.

In its proposal, the French Agency for Food, Environmental and Occupational Health and Safety (Anses) argues for the classification based on lung cancers formed in rats after inhalation. The authors review two oral studies but find that uptake in the gut is “rather limited”, although they concede some titanium dioxide particles may be better absorbed, depending on their size and coating.

Their overall conclusion is that “no concern has been identified after oral exposure”.

New findings

The latest research, conducted by the French National Institute of Agricultural Research (Inra), suggests the situation is more complicated, particularly in relation to gut absorption. The researchers report on short- and long-term exposures of rats to food-grade titanium dioxide at levels similar to those in the human diet.

Food-grade titanium dioxide, also known as E171, is widely used in foods and confectionery as a whitening agent and contains nanoparticles with diameters below 100nm.

The researchers found that the particles crossed the rat gut barrier and reached the liver. They were also found in the lymphoid tissue of the small intestine, where they upset the immune system by altering the number of dendritic cells and triggering imbalances in immune responses.

The researchers say that oral studies have so far mainly used titanium dioxide nanoparticles with a different particle size-range to E171, such as NM-105 on the EU Joint Research Centre database. E171 has primary particles with diameters ranging from 30 to 400nm they say, with only about 36% of particles falling below the 100nm nanomaterial threshold.

They conclude: “The daily consumption of E171-containing food may constitute a persistent source for the systemic passage of titanium dioxide nanomaterials and that particles sequestered into the gut mucosa represent an unexplored topic for in vivo toxicity assessments of food-grade titanium dioxide.”

Regulatory context

The Scientific Panel on Food Additives and Nutrient Sources added to Food, at the European Food Safety Authority, published an opinion on the safety of titanium dioxide as a food additive in September 2016.

The panel concluded that – based on the available data – “absorption of orally administered [titanium dioxide] is extremely low and the low bioavailability of [titanium dioxide] appears to be independent of particle size”. They added that the substance did not “raise a genotoxic concern”.

But after the latest research appeared, the French Ministries for Consumer affairs, Health and Food asked Anses to determine the feasibility of a risk assessment of E171. This will be conducted as part of a broader assessment of the human health risks of nanomaterials in food, launched in October 2016.

Meanwhile, Echa’s Risk Assessment Committee (Rac) is expected to formally discuss the classification proposal in June and produce an opinion by the end of this year. The June discussions will be preceded by a key issues debate, at the committee's meeting in March.

Echa told Chemical Watch that “Rac will take into account all relevant scientific information that is available to the committee,” including information provided in the French authority's proposed classification report, and that it received during the public consultation. Information received after this that is “new and relevant” may also be considered by the committee “on a case-by-case basis”.

Asked whether Rac had a mandate to give an opinion on oral exposure, despite the conclusions in the proposal, the agency said: “Rac may or may not adopt the classification proposed in the French classification report. It will provide an independent scientific opinion, based on all relevant scientific information that is available to the committee.”

Industry groups have strongly opposed the proposal on the basis that the rat data, underpinning the inhalation hazard assessment, are not relevant.

The Titanium Dioxide Manufacturers Association (TDMA) said that “the tests found no consistent pattern”. Furthermore, the protocol could not be “extrapolated to conclude that [titanium dioxide] could cause cancer in humans.

“In fact, Inra clearly states that its findings cannot be extended to draw conclusions for human health, and that they do not comply with OECD guidelines for the testing of chemicals. Other studies carried out in conformity with OECD guidelines have not shown any adverse effect at doses considerably higher than those used in the Inra study.”